title: Physics-based method to validate and repair flaws in protein structures.
abstract: A method that makes use of information provided by the combination of (13)C(α) and (13)C(β) chemical shifts, computed at the density functional level of theory, enables one to (i) validate, at the residue level, conformations of proteins and detect backbone or side-chain flaws by taking into account an ensemble average of chemical shifts over all of the conformations used to represent a protein, with a sensitivity of ∼90%; and (ii) provide a set of (χ1/χ2) torsional angles that leads to optimal agreement between the observed and computed (13)C(α) and (13)C(β) chemical shifts. The method has been incorporated into the CheShift-2 protein validation Web server. To test the reliability of the provided set of (χ1/χ2) torsional angles, the side chains of all reported conformations of five NMR-determined protein models were refined by a simple routine, without using NOE-based distance restraints. The refinement of each of these five proteins leads to optimal agreement between the observed and computed (13)C(α) and (13)C(β) chemical shifts for ∼94% of the flaws, on average, without introducing a significantly large number of violations of the NOE-based distance restraints for a distance range ≤ 0.5 , in which the largest number of distance violations occurs. The results of this work suggest that use of the provided set of (χ1/χ2) torsional angles together with other observables, such as NOEs, should lead to a fast and accurate refinement of the side-chain conformations of protein models.
authors.affiliation: Instituto de Matemática Aplicada San Luis, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Departamento de Física, Universidad Nacional de San Luis, 5700 San Luis, Argentina.
authors.forename: Osvaldo A
authors.initials: OA
authors.lastname: Martin
authors.forename: Yelena A
authors.initials: YA
authors.lastname: Arnautova
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Icazatti
authors.forename: Harold A
authors.initials: HA
authors.lastname: Scheraga
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Vila
mesh_terms: D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins